This is a Shannon Award providing partial support for the research projects that fall short of the assigned institute's funding range but are in the margin of excellence. The Shannon Award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. The long term objectives of these studies are to elucidate mechanisms controlling the entry of T lymphocytes into sites of inflammation. Part of the underlying hypothesis of the proposed studies is that central to the accumulation of alpha/beta TCR(+) T cells in tissue is the extravasation of gamma/delta TCR((+) T cells. Thus, gamma/delta T cells appear in tissue, such as rheumatoid synovial membrane, early and they may initiate mechanisms that subsequently lead to the extravasation into tissue of alpha/beta TCR(+) T cells, and thus play a critical role in the immunologically mediated inflammatory responses. Experiments will test the hypothesis that by a mechanism similar to that used by neutrophils, constitutively active adhesion receptors, such as L-selectin, mediate the initial interactions of gamma/delta T cells with the endothelium in the absence of marked inflammation when blood flow is intact, and that subsequent stabilization of adhesion by integrin adhesion receptors may allow transendothelial migration of gamma/delta T cells into the tissue. Experiments will also determine whether the transendothelial migration of gamma/delta T cells is regulated by specific chemotactic factors and/or the subendothelial extracellular matrix. Finally, experiments will determine whether a result of the appearance of gamma/delta T cells in tissue and activation are phenotypic and functional changes in the endothelium such that the transendothelial migration of alpha/beta T cells into inflamed tissue is facilitated. Such mechanisms may, therefore, play a prominent role in establishing immunologically mediate inflammation.